This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Neutralizing antibodies are important for HIV vaccines. Passive antibody transfer has shown that neutralizing antibodies, at high concentrations, protect from vaginal challenge with pathogenic SHIVs bearing the HIV-1 envelope. The mechanisms of protection by neutralizing antibody and in particular, the role of Fc-mediated effector function have not been defined. The role of secretory IgA and the interplay between mucosal and systemic neutralizing antibodies is probably important but has not been studied. In 2007 and 2008, a low-dose, repeated exposure experiment was conducted. A total of 17 animals were treated weekly with intravenous antibody and challenged twice weekly intravaginally with SHIV 162p3 until infection was confirmed and/or bDNA. All animals were treated with Depo-provera 35 days prior to the first challenge and every 21 days thereafter to maintain a thinned vaginal epithelium. Control animals (n=7) were treated with control (PBS) antibody at a dose equivalent to 1 ml/kg. Animals in the LL mutant group (n=5) and the b12 wild type group (n=5) were treated with their respective antibodies at a dose of 1 ml/kg. Challenge doses ranged from 3 TCID50 to 29 TCID50. All control animals became infected after a range of challenges from 8[unreadable]16 (average = 11.7+/- 3.1 SD). All LL mutant animals became infected after a range of challenged from 17[unreadable]36 (average = 26.8 +/- 9.5 SD). 4 of 5 b12 animals became infected after a range of challenges from 8-50 (average = 27.8 +/- 18.9 SD). The final b12 animal resisted infection after 56 challenges (6 of those without antibody treatment).